Structure of the quaternary complex of histone H3-H4 heterodimer with chaperone ASF1 and the replicative helicase subunit MCM2 - PubMed (original) (raw)

Structure of the quaternary complex of histone H3-H4 heterodimer with chaperone ASF1 and the replicative helicase subunit MCM2

Hong Wang et al. Protein Cell. 2015 Sep.

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Figure 1

Figure 1

Structure of the MCM2-ASF1-H3-H4 complex. (A) Schematic diagram showing the truncated fragments of the four proteins. MCM2, ASF1, H3 and H4 are shown in yellow, green, cyan and magenta respectively (color coded the same in all figures). Disordered regions in the structure are shown in gray. An image of the coomassie-stained SDS-PAGE gel of the purified complex showing apparent stoichiometry of the four proteins. MCM2 appears to have an anomalous SDS-PAGE migration profile, as a Mass spectrometric measurement indicates a molecular weight 10,774 Da (data not shown). (B) A ribbon diagram showing the overall structure of the quaternary complex. (C) Interactions between MCM2 and H3-H4 heterodimer. The structure of MCM2 from the ternary MCM2-H3-H4 structure (PDB code: 4UUZ, shown in gray) is superimposed for comparison. Three panels indicate N-terminal, middle and C-terminal binding regions of MCM2. Residues involved in intermolecular interactions are shown in a stick model (carbon, yellow, magenta and cyan; nitrogen, blue; oxygen, red). Dashed lines indicate intermolecular hydrogen bonds. (D) Interactions between ASF1 and histone H3. Superposition of ASF1 and H3 from our quaternary structure and that from the ternary ASF1-H3-H4 structure (PDB code: 2HUE, shown in gray). C-terminal ends of ASF1 in the two structures and α2 MCM2 are highlighted inside the red circle. (E) Interactions between ASF1 and histone H4. The βC strand of H4 in the MCM2-H3-H4 ternary structure and in a human nucleosome structure (shown in gray and magenta, respectively) are aligned with that in the quaternary structure. Histone H2A in the nucleosome structure are shown in red. (F) Direct interactions between MCM2 and ASF1

Figure 2

Figure 2

Possible biological functions of the MCM2-ASF1-H3-H4 complex. (A) The binding of MCM2 and ASF1 obstructs the formation of NCP and a histone (H3-H4)2 tetramer. A human nucleosome structure (PDB code: 2CV5, shown in gray) is aligned with the MCM2-ASF1-H3-H4 structure via the H3-H4 heterodimer. Four obstructed regions are enclosed in red circles and numbered according to the order in which they were referenced in the text. (B) A model of possible biological functions of the MCM2-ASF1-H3-H4 quaternary complex in the cytoplasm and in the nucleus. The cytosolic MCM2 may facilitate nuclear import of histones H3 and H4. In the nucleus, ASF1 “hands” the H3-H4 heterodimer to the CAF-1 complex prior to the deposition onto replicated DNA, in the presence or absence of MCM2. The ASF1-H3-H4 complex might also be directly recruited to the replication fork by interaction with the MCM complex

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